Chronic exposure to palmitate impairs fatty acid oxidation and insulin‐stimulated glucose uptake despite activation of AMPK in skeletal muscle cells
Bibliographic record
Abstract
The aim of this study was to investigate the chronic effects of palmitate on fatty acid oxidation, AMPK/ACC phosphorylation/activation, intracellular lipid accumulation, and the molecular mechanisms involved in these processes in skeletal muscle cells. Exposure of L6 myotubes for 8h to 200, 400, 600, and 800uM of palmitate reduced fatty acid oxidation by ∼26.5%, ∼43.5%, ∼50%, and ∼47%, respectively. Interestingly, this occurred despite significant increases in AMPK (∼2.5‐fold) and ACC (∼3‐fold) phosphorylation and in malonyl‐CoA decarboxylase activity (∼38% – 60%). Low concentrations of palmitate (50–100uM) caused an increase (∼30%) in CPT‐1 activity. However, as the concentration of palmitate increased, CPT‐1 activity decreased by ∼32% after exposure for 8h to 800uM of palmitate. Although fatty acid uptake was reduced (∼35%) in cells exposed to increasing palmitate concentrations, intracellular lipid accumulation increased in a dose‐dependent manner, reaching values ∼2.3‐, ∼3‐, and 4‐fold higher than control in muscle cells exposed to 400, 600, and 800uM palmitate, respectively. This was accompanied by a progressive and time‐dependent inhibition of glucose uptake (∼65%) in myotubes. These findings may help explain the dysfunctional adaptations that occur in glucose metabolism in skeletal muscle under conditions of chronically elevated levels of NEFAs, such as in obesity and type 2 diabetes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".